rEvIEWS - Advances in Clinical and Experimental Medicine

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Adv Clin Exp Med 2012, 21, 5, 671–680
ISSN 1899–5276
© Copyright by Wroclaw Medical University
Franciszek IwańczakA–F, Barbara IwańczakA–F
Treatment of Helicobacter pylori Infection in the Aspect
of Increasing Antibiotic Resistance
Leczenie zakażenia Helicobacter pylori w świetle narastającej oporności
na antybiotyki
Department of Pediatrics, Gastroenterology and Nutrition, Wroclaw Medical University, Poland
A – research concept and design; B – collection and/or assembly of data; C – data analysis and interpretation;
D – writing the article; E – critical revision of the article; F – final approval of article; G – other
Abstract
In the present work, the problem of Helicobacter pylori infection in the world and its increasing antibiotic resistance are analyzed. The authors discuss the efficacy of treatment, noting that the clarithromycin – and metronidazole-resistance of H. pylori is the main cause of this treatment failure. Because of this phenomenon, a quadruple
therapy is being introduced and clarithromycin is being replaced by new antibiotics. The authors also present various schemes of triple and quadruple therapy as well as sequential therapy. Attention is directed to the fact that, in
order to obtain better results of the eradication, the treatment should be prolonged from 7 to 10 or even 14 days,
and that the doses of the drugs should be increased (Adv Clin Exp Med 2012, 21, 5, 671–680).
Key words: Helicobacter pylori, resistance, treatment, sequential therapy.
Streszczenie
W pracy przedstawiono problem zakażenia Helicobacter pylori na świecie oraz narastającą oporność H. pylori na
antybiotyki stosowane w leczeniu zakażenia. Autorzy omawiają skuteczność leczenia zakażenia, zwracając uwagę, że
przyczyną niepowodzenia eradykacji jest oporność H. pylori na stosowaną w leczeniu klarytromycynę i metronidazol. Z tego powodu wprowadza się terapię czteroskładnikową, zastępuje się klarytromycynę nowymi antybiotykami.
Wprowadza się do leczenia sole bizmutu. Autorzy przedstawiają różne schematy terapii trójskładnikowej i czteroskładnikowej oraz leczenie sekwencyjne. W celu osiągnięcia lepszych wyników eradykacji wydłuża się czas leczenia
z 7 do 10 lub 14 dni, a także zwiększa dawki stosowanych leków (Adv Clin Exp Med 2012, 21, 5, 671–680).
Słowa kluczowe: Helicobacter pylori, oporność, leczenie, terapia sekwencyjna.
Helicobacter pylori (H. pylori) infection is one
of the most common infections worldwide. The
frequency of H. pylori infection is variable and
depends on age, ethnicity, gender, geography and
socioeconomic status. Most of the infected people
are living in developing countries in Africa, South
America and Asia. The lowest rate of infection is
observed in Australia, Canada and the USA. A high
rate of small children among infected patients in
developing countries draws attention. In Bangladesh, the rate of infected children younger than
two years has reached 50–60%, in Ethiopia among
children aged two to four years, the infection rate is
48%, and in Egypt 50% of three-year-old children
are infected. The infection rate in these countries
exceeds 90% in adults [1]. Table 1 presents the frequency of H. pylori infection in children and adults
in selected countries. In Europe, the highest rate of
infection is observed in Poland, Albania and Estonia and the lowest in Sweden and Switzerland.
The highest number of infected children is noted
in Bulgaria (Table 2) [1, 2].
Helicobacter pylori colonizes gastric mucosa.
The possibility of H. pylori survival in the gastric
acidic environment is possible due to urease production, an enzyme giving protection against the
672
F. Iwańczak, B. Iwańczak
acidic environment by hydrolysis of the urea to
carbon dioxide and ammonia that neutralizes acid.
The discovery by Marshall and Warren in 1983 of
Helicobacter pylori bacteria in the human stomach with chronic gastritis and peptic ulcerative
disease has changed the viewpoint on the ethiopathogenesis of upper gastric diseases and their
management [3] H. pylori infection evokes the inflammation of gastric mucosa. The inflammatory
process is of a chronic and progressive character
and may, after many years, lead to the atrophy of
mucosa, ulcerative disease of the stomach and/or
duodenum, metaplasia, dysplasia, gastric cancer,
and gastric MALT lymphoma (mucosa-associated
lymphoid tissue). The development of the abovementioned diseases depends on the genotype of
H. pylori and bacterial virulence connected with
this genotype [4, 5]. Numerous studies have confirmed that the composition of s1m1 alleles in the
VacA gene is typical for most virulent strains. The
CagA gene codes the immunogenic protein with
potent inflammatory properties. The induction
of the inflammatory process, the development of
peptic ulcerative disease, neoplastic transformation and the natural course of infection strongly
depend on the genome of the H. pylori strain. It
has been demonstrated that the H. pylori genotype
cagA(–), vacA(–) has a low pathogenicity and does
not lead to neoplastic diseases [6–8].
Table 1. Prevalence of Helicobacter pylori infection in the world (acc. 1)
Tabela 1. Częstość występowania zakażenia Helicobacter pylori na świecie (wg 1)
Country (Kraj)
Ethiopia
Nigeria
Egypt
Mexico
Canada
USA and Canada
Brazil
Chile
Bangladesh
India
Japan
South Korea
Taiwan
Australia
Turkey
Age (years) and prevalence (Wiek – lata i częstość występowania)
children
prevalence %
adults
prevalence %
2–4
5–9
3
5–9
5–18
48
82
50
43
7.1
6–8
10–19
3–9
0–2
8–9
0–4
10–19
30
78
36
50–60
82
22
87
adults
adults
adults
adults
50–80
adults
adults
> 95
70–90
90
70–90
23.1
30
82
adults
70–90
adults
> 90
16
9–12
1
6–17
56
11
adults
20–70
88
55.4
>25
59
adults
45.1
15.4
80
64%
Table 2. Prevalence of Helicobacter pylori infection in Europe (acc. 1, 2)
Tabela 2. Częstość występowania zakażenia Helicobacter pylori w Europie (wg 1, 2)
Country (Kraj)
Albania
Bulgaria
Czech Republic
Estonia
Germany
Iceland
Netherlands
Poland
Sweden
Switzerland
Age (years) and prevalence (Wiek – lata i częstość występowania)
children
prevalence %
1–17
61.7
2–4
0–18
1.2
32.01
adults
prevalence %
16–64
70.7
5–100
25–50
50–74
25–50
42.1
69
48.8
36
19–89
25–50
18–85
84.19
11
11.9
37.8
Clarithromycin
69.7
36.4
38.2
Metronidazole
Levofloxacin
Moxifloxacin
6.6
Rifampicin
Clarithromycin and
metronidazole
Furazolidone
2.5
Gentamycin
Ciprofloxacin
2.3
Tetracycline
Azithromycin
4.9
China
Song et al.
[10] – 2011
%
Country (Kraj )
Amoxicillin
Antibiotic
(Antybiotyk)
10.2
33.5
0.6
6.6
0.6
Taiwan
Wu et al.
[11] – 2010
%
0
85
7
0
0
India
acc. [1]
– 2005
%
5.3
47.1
1.9
3
5.6
Mahachaj et al.
[12]
Thailand
– 2011
%
Tabela 3. Oporność Helicobacter pylori na antybiotyki na świecie (wg 1, 10–15)
Table 3. Antibiotic resistance of Helicobacter pylori in the world (acc. 1, 10–15)
2
100
4
2
Egypt
acc. [1]
– 2004
%
53
9
Brazil
acc. [1]
– 2002
%
32.4
45.1
0
8.8
10.8
Korea
Moon et al.
[15]
– 2011
%
4
15
0
15
0
Children.
in European
Centers
– 2011 [13]
%
5.3
23
0
24
0
Children.
Sixteen
European
Centers
– 2006 [14]
%
0.2
28.1
45.3
Children.
Greece – 2011
[16]
%
H. pylori and Increasing Antibiotic Resistance
673
674
F. Iwańczak, B. Iwańczak
Treatment of Helicobacter
pylori Infection
The discovery of Helicobacter pylori caused
a breakthrough in the treatment of the diseases of
the stomach and duodenum. These diseases can be
treated or prevented by eradication of the H. pylori infection which can be regarded as a causative
factor. An acceptable efficacy of H. pylori eradication of more than 80% can by achieved using
treatment with three or four drugs concomitantly.
Among these drugs are substances decreasing gastric secretion, most often a proton pump inhibitor PPI, antibiotics: amoxicillin, clarithromycin,
tetracycline, chemotherapeutics: metronidazole
or tinidazole, levoflaxacine, moxifloxacine, furazolidone and bismuth salts. The efficacy of various treatment schemata depends on the H. pylori
sensitivity to the antibiotics and chemotherapeutics used, the selection of the drugs in the schema,
the duration of treatment and patient adherence to
a recommended treatment regimen.
Helicobacter pylori
Antibiotic Resistance
In the last decade, unsatisfactory results of
H. pylori eradication with proton pump inhibitors, amoxicillin and clarithromycin have been observed. In 2008, Graham and Shiotaniu presented
the results of treatment of 9000 patients with Helicobacter pylori infection. The authors of that study
have demonstrated that the rate of eradication with
the above described regimen was unsatisfactory. In
the USA, Europe, Japan, Korea and China it was below 80%. In contrast, the eradication rate obtained
in Hong Kong and Singapore was above 80% [9)]
The principal cause of H. pylori treatment failure is
a high clarithromycin resistance [10–14]. Table 3
summarizes H. pylori resistances to drugs used in
various countries of the world. A high H. pylori
resistance to clarithromycin (37.8%), azithromycin (49.8%), metronidazole (69.7%), levofloxacin
(36.5%) and moxifloxacin (38.2%) exists in China
(10). In Taiwan there is a high resistance to metronidazole (85%), similar to in Egypt (100%), Brazil
(53%) and Thailand (47.1%) [1, 11]. Studies conducted by Moon et al. have demonstrated frequent
H. pylori resistance to drugs used in eradication in
South Korea which differs from that in Europe [15].
Studies on H. pylori resistance conducted in South
Korea have demonstrated H. pylori resistance to
amoxicillin – 10.8%, clarithromycin – 8.8%, metronidazole – 45.1%, levofloxacin – 32.4% and 0% to
tetracycline [15]. In multicenter studies conducted
in China by Song et al., a high resistance was demonstrated not only to clarithromycin (37.8%), metronidazole (69.7%), levofloxacin (36.4%), azithromycin (49.8%) and moxifloxacin (38.2%), but also
to amoxicillin (4.9%), tetracycline (2.3%), gentamycin (2.5%) and rifampicin (6.6%). In children
living in Greece, high resistance to clarithromycin
(45.3%) and metronidazole (28.1%) has been observed. According to Mégraud, H. pylori resistance
in particular European countries and in other parts
of the world is different and depends on the use of
antibiotics in the treatment of other diseases in various regions [17].
In European countries, H. pylori clarithromycin resistance amounts to 5–28%, and metronidazole resistance to 20–40%. In Europe, H. pylori
resistance to amoxicillin and tetracycline, which is
present at a low rate in China and Thailand, is not
noted. Koletzko et al. analyzed H. pylori resistance
in children in 14 countries in Europe and observed
clarithromycin resistance reaching up to 24%, but
was different in various countries [14]. In Poland,
the studies conducted by Dzierżanowska-Fangrat
et al. in 2005 have demonstrated the resistance to
clarithromycin to be 28% in children and 15% in
adults. Resistance to metronidazole was high and
equal to 40% and 42% in children and adults, respectively. Double resistance to clarithromycin
and metronidazole was observed in 20% of patients. Resistance to amoxicillin, ciprofloxacin and
tetracycline has not been observed [18]. Gościniak
et al. demonstrated an increasing H. pylori resistance in children in Lower Silesia [19, 20]. In the
years 1997–2000 primary H. pylori resistance to
clarithromycin was 5.7% and to metronidazole
30.4%. Resistance checked four to six weeks after
completion of treatment was 15.7% to clarithromycin and 51% to metronidazole. A study conducted
in the years 2007–2008 has demonstrated an increase in the primary resistance to clarithromycin
to 24% and to metronidazole to 32%. Moreover,
an increase in the resistance of H. pylori after the
first unsuccessful treatment with metronidazole
and clarithromycin has been observed. Similar results of studies on primary and secondary H. pylori
resistance were obtained by Koletzko et al. [14].
These authors have demonstrated an increase in
secondary resistance to clarithromycin from 23 to
35% and to metronidazole from 20 to 42%. Secondary resistance to both drugs also increased,
from 5.3 to 15.3% [14]. The latest studies on primary H. pylori resistance in Poland using the Etest method in the years 2009–2011 in adults aged
19–89 years with functional dyspepsia have demonstrated a resistance to clarithromycin to be 24%,
to metronidazole – 68% and to levofloxacin – 8%.
Resistance to more than one antibiotic was 26%
675
H. pylori and Increasing Antibiotic Resistance
and the resistance to clarithromycin and metronidazole together – 20%. No resistance to rifamipicin, tetracycline and amoxicillin has been observed
[21]. Epidemiological studies on H. pylori infection
in Poland have proved significant regional differences in H. pylori resistance to clarithromycin
and metronidazole. Resistance to clarithromycin
in children ranged from 9 to 29% and in adults
from 3 to 27% and resistance to metronidazole in
children from 16 to 43% and in adults from 27 to
52% [2]. H. pylori resistance in children in Poland
is presented in Table 4.
The issue of H. pylori resistance to the drugs
used is important for obtaining efficient eradication. Fischbach and Evans, by analyzing the influence of H. pylori resistance on the efficacy of
eradication, demonstrated that in triple therapy,
clarithromycin resistance diminished this efficacy
of eradication by 66% and metronidazole resistance by 14%. In quadruple therapy consisting of
a proton pump inhibitor, amoxicillin, clarithromycin and metronidazole, the influence of H. pylori
resistance to clarithromycin and to metronidazole
was smaller [22]. Moon et al. demonstrated a significant influence of clarithromycin resistance on
the diminishing of the H. pylori eradication index
[15]. The authors demonstrated that the success of
H. pylori infection therapy consisting of a proton
pump inhibitor, amoxicillin and clarithromycin as
well as of sequential therapy with metronidazole
for ten days depended mainly on H. pylori sensitivity to clarithromycin [15].
Sequential Therapy
In recent years, reports demonstrating the superiority of sequential administration of drugs in
H. pylori infection therapy have been published. In
sequential therapy, the manner of drug administration has been changed. During the 10-day therapy,
a proton pump inhibitor and amoxicillin is given
for the first five days and is followed by a proton
pump inhibitor, clarithromycin and metronidazole
for the subsequent five days. The results of treatment following this schema are diverse. Graham
and Shiotari analyzed the results of 16 studies of
sequential therapy conducted for 10 days in 1805
patients and nine studies on parallel administering
of the same drugs (PPI, amoxicillin, clarithromycin and metronidazole for 3–7 days) in 715 patients
[9]. The intention to treat index was similar and
was 93.4% vs. 91.7%. Recent studies emphasize that
the efficacy of sequential therapy depends on H. pylori resistance to clarithromycin and metronidazole
as well as on the compliance of patients. Schwarzer
et al. evaluated the efficacy of sequential therapy in
160 children from nine European countries with an
average age of 12.3 years [13]. The therapy encompassed: esomeprazole – 1 mg/kg/day and amoxicillin 50 mg/kg/day for five days and for the next five
Table 4. Antibiotic resistance of Helicobacter pylori in Poland (acc. 2, 18–21)
Tabela 4. Oporność Helicobacter pylori na antybiotyki w Polsce (wg. 2, 18–21)
Dzierżanowska-Fangart et al.
[18] Warsaw 2005
Gościniak et al. [19–21]
Lower Silesia
Łaszewicz [2]
Poland 2004
children
adults
children
(2007–2008)
adults
(2011)
children
adults
Amoxicillin
0
0
0
0
0
0
Clarithromycin
29%
15%
24%
24%
20%
(9–26%)
15%
(3–27%)
Tetracycline
0
0
0
0
0
0
Metronidazole
40%
42%
F/M
58.5% vs 37%
32%
68%
27%
(16–43%)
42%
(27–52%)
10%
(0–16%)
8%
(3–11%)
Levofloxacin
8%
Moxifloxacin
Gentamycin
Rifampicin
Clarithromycin
and metronidazole
0
20%
F – female (kobiety), M – male (mężczyźni).
20%
676
F. Iwańczak, B. Iwańczak
Table 5. Comparison of diagnostic tests for Helicobacter pylori infection (acc. 1)
Tabela 5. Porównanie testów diagnostycznych w rozpoznawaniu zakażenia Helicobacter pylori (wg 1)
Test (Test)
Sensitivity
(Czułość)
Specificity
(Swoistość)
Positive predictive value
(Dodatnia
wartość
predykcyjna)
Comments (Komentarz)
Rapid urease test (Szybki test ureazowy)
> 98%
99%
99%
rapid and cheap
Histology (Histologia)
> 95%
>95%
detection improved by use of
special stains
Culture (Hodowla)
highly specific
PCR
sensitive and specific
ELISA serology
85–92%
79–83%
64%
does not identify active infection
13 or 14 C urea* breath test
(Ureazowy test oddechowy)
85%
96%
88%
recommended for diagnosis
Stool antigen (Antygen w kale)
95%
94%
84%
inexpensive and noninvasive
Finger-stick serology test (Testy
serologiczne krwi)
very poor
PCR – polymerase chain reaction.
PCR – polimerazowa reakcja łańcuchowa.
ELISA – enzymatyczny test immunoabsorbcyjny.
ELISA – enzyme-linked immunosorbent assay.
* Recommended for diagnosis of Hp before treatment and for confirming eradication.
* Zalecany do diagnostyki przed leczeniem i do potwierdzenia eradykacji.
days: esomeprazole, clarithromycin (25 mg/kg/day)
and metronidazole (25 mg/kg/day) in two divided
doses. In all children, the diagnosis of the H. pylori
infection was based on a culture. H. pylori resistance to the antibiotics was also examined. Primary
clarithromycin resistance was 15%, metronidazole
resistance was also 15% and resistance to both antibiotics was 4%. The index of H. pylori eradication
was 82% (131/160) and was significantly higher if
the H. pylori strains were sensitive to clarithromycin and metronidazole and amounted, in this case,
to 91%. In the case when clarithromycin resistance
was present, this index was only 70%, in the case of
metronidazole resistance – 67% and in resistance to
both antibiotics – 29%.
Wu et al., in a randomized study, compared the
efficacy of sequential and parallel treatment (concomitant therapy with four drugs) of H. pylori infection for 10 days [11]. The concomitant therapy
consisted of omeprazole 40 mg, amoxicillin 1000
mg, clarithromycin 500 mg and metronidazole
500 mg given twice a day for 10 days or 10-days sequential therapy (esomeprazole 40 mg, amoxicillin
1000 mg twice a day for five days and esomeprazole
40 mg, clarithromycin 500 mg and metronidazole
twice a day to complete the 10 day therapy). An
intention to treat analysis has demonstrated simi-
lar eradication rates for sequential (92.3%; 95%
CI:87.5–97.1%) and concomitant therapy (93.0%,
95% CI:88.3%–97.7%). Resistance to clarithromycin, compliance and adverse events reduced the
level of eradication. Univariate analysis showed
that compliance and resistance to clarithromycin
were independent determinants of eradication.
According to the authors, concomitant therapy
is more suitable for areas with dual resistance to
antibiotics [11]. The results of these studies are in
concordance with guidelines of pediatric scientific
societies (ESPGHAN and NASPGHAN) [23]. In
a population with high resistance to clarithromycin, exceeding 20% in first line therapy, this antibiotic usage should be reduced or H. pylori resistance should be determined and antibiotics should
be used according to it [23].
Indication for Eradication
Treatment of Helicobacter
pylori Infection in Children
and Adults
The indication for diagnosis and treatment of
H. pylori infection are proposed by experts of scien-
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H. pylori and Increasing Antibiotic Resistance
Table 6. Treatment options of Helicobacter pylori infection (acc. 1, 24)
Tabela 6. Leczenie zakażenia Helicobacter pylori infection (wg 1, 24)
Therapy (Leczenie)
Treatment options (Schematy leczenia)
Notes (Uwagi)
First-line therapies (resistance to clarithromycin is not known) (Pierwsza
linia leczenia)
PPI + Amx + Met
PPI + Cl + Met
PPI + Amx + Cl
twice daily for 7, 10 or 14 days
(1)
Triple-therapy treatment regimens:
PPI + 2 antibiotics: Amx and Cl, or
Met and Cl
sequential therapy: 10 day therapy with PPI
+ Amx for 5 days and PPI + Cl + Met for
5 days
eradication rates 70–85%
(increasing resistance to clarithromycin)
In case of a clarithromycin resistance
rate of more than 20%:
Quadruple therapy:
PPI + Bismuth + 2 antibiotics:
Amx + Cl or Met + Tet
quadruple therapy:
PPI b.i.d. + Amx + Met + Tet ** all. q.i.d.
PPI+ Bismuth + Amx + Met
PPI + Bismuth + Tetr + Met
for 7, 10 or 14 days
Second-line therapies (after failure of
clarithromycin-containing regimen)
(Druga linia leczenia)***
PPI + Bismuth + Tet + Met
PPI + Amx + Lev
PPI + Fur + Tet + Bismuth
PPI + Fur + Lev
for 10–14 days
for 10 days
for 10 days
for 10 days
Third-line therapies
(Trzecia linia leczenia)
Sensitivity determination of H. pylori
to Amx, Cl, Met, Lev, Tetr
treatment according to sensitivity of
H. pylori to antibiotics
b.i.d. bis in die (twice a day), q.i.d. quater in die (four times a day).
PPI – proton-pump inhibitor*; Amx – amoxicillin; Cl – clarithromycin; Met – metronidazole; Tet – tetracycline; Lev – levofloxacin; Fur – furazolidone.
* Conventional dosage: Omeprazole 20 mg, Lanzoprazole 30 mg, Pantoprazole 40 mg, Esomeprazole 40 mg.
* Dawkowanie: Omeprazole 20 mg, Lanzoprazole 30 mg, Pantoprazole 40 mg, Esomeprazole 40 mg.
** Tetracyclin should not be used in children under 9 years of age.
** Tetracykliny nie należy stosować u dzieci poniżej 9 lat.
*** In children, the determination of sensitivity of H. pylori to claritromycine is recommended [23].
*** U dzieci zaleca się badanie wrażliwości H. pylori na klarytromycynę.
Table 7. Dosage of the medicine used in children
Tabela 7. Dawkowanie leków stosowanych u dzieci
Omeprazole
1 mg/kg of body weight per 24h, maximum 20 mg/24h twice daily
Amoxicillin
50 mg/kg of body weight per 24h, maximum 1000 mg/24h b.i.d.
Clarithromycin
15 mg/kg of body weight per 24h, maximum 500 mg/24h twice daily
Metronidazole or tinidazole
20 mg/kg of body weight per 24h, maximum 500 mg/24h twice daily
Bismuth salts
8 mg/kg of body weight per 24h, 2 or 4 times per 24h, maximum 2 or 4 × 120 mg
four times daily, (maximum 480 mg/24h)
Tetracycline*
25–50 mg/kg of body weight/24hour, maximum 250 mg four times daily
* May by used after the 9th year of life.
* Może być stosowany po 9. roku życia.
tific societies all over the world [23–26]. According
to the accepted consensus, diagnostic procedures
toward H. pylori infection in children should be
undertaken if symptoms suggest the presence of organic disease and are an indication for esogastroduodenoscopy with sampling of the gastric mucosa.
The Working Group of the Polish Society of
Gastroenterology prepared the guidelines for in-
dications for eradicative therapy [24]. Indications
for the treatment of Helicobacter pylori infection
in children are: active or previous gastric and duodenal ulcer, chronic gastritis independent of the
stage, long term NSAID (not-steroidal anti-inflammatory drug) use, immunosuppressive treatment, anemia due to iron deficiency for unknown
reasons and idiopathic thrombocytopenia.
678
F. Iwańczak, B. Iwańczak
Table 8. Dosage of the medicine used in adults
Tabela 8. Dawkowanie leków u dorosłych
Medicine (Lek)
Dosage (Dawkowanie)
Omeprazole
Lanzoprazole
Pantoprazole
Rabeprazole
Esomeprazole
Amoxicillin
Clarithromycin
Tetracycline
Metronidazole or
tinidazole
Levofloxacin*
Moxifloxacin**
Bismuth salts
Furazolidone
20 mg/twice a day
30 mg/twice a day
40 mg/twice a day
20 mg/twice a day
40 mg/twice a day
1000 mg/twice daily
500 mg/twice daily
250 mg/four times daily
500 mg/twice daily
500 mg/twice daily
400 mg/twice daily
120 mg/four time daily
100 mg/four time daily
* tuberculostatic.
* przeciwprątkowy.
** should not by used until the 18th year of life.
** nie należy stosować do 18. roku życia.
Indications for the eradicative treatment of
H. pylori infection in adults are: active, previous
or postoperative duodenal and/or gastric ulcer,
gastritis (exacerbated by aphtae), atrophic gastritis, metaplasia, dysplasia, gastric resection due to
premature cancer, gastric cancer in the family, adenomatous and hyperplastic polyps (after removing them), MALT (mucosa associated lymphoid
tissue) lymphoma, Menetrier’s disease, functional
dyspepsia, long term NSAID treatment and at the
patients request (after consulting a doctor). The
utility of the suggested diagnostic tests is presented
in Table 5.
Options for the Treatment
of H. pylori Infection
In literature from all over the world, the efficacy
of eradications with various schemes of treatment is
described. In the case of an unknown sensitivity of
H. pylori to clarithromycin, treatment with a proton pump inhibitor and two antibiotics: amoxicillin
and metronidazole or clarithromycin and metronidazole or amoxicillin and clarithromycin, as well as
sequential therapy for 10 days is advised. The duration of a triple therapy should be 7, 10 or 14 days. If
in a certain region the resistance to clarithromycin
is higher than 20%, or even, according to Romano
et al., higher than 15%, the scheme of treatment
should be modified. Quadruple therapy should be
introduced, clarithromycin should be replaced with
bismuth salts or tetracycline or levofloxacin and
the duration of therapy should be prolonged to 10
or even 14 days [1, 23–30]. After a failure of that
treatment, the sensitivity of H. pylori to antibiotics should be determined and H. pylori infection
should be treated according to the results of this
determination. The proposed schemes of treatment
are presented in Table 6. It should be noted that tetracyclines should not be given to children younger
than nine years and that levofloxacin is tuberculostatic and is not accessible in Poland. Tables 7 and
8 present the dosage of drugs in children and adults.
Schwarzer et al., in a case of 62 children with double
resistance (to clarithromycin and metronidazole),
used a 14-day therapy with increased doses of a proton pump inhibitor, amoxicillin and metronidazole.
They have obtained an eradication rate of 73% (per
protocol, mild to moderate adverse events were reported by 21 children). Among the most frequent
adverse events were nausea, diarrhea and vomiting
(Table 9) [31].
Table 9. Treatment of H. pylori infection with double resistance in 62 children [31]
Tabela 9. Dawkowanie leków w leczeniu zakażenia H. pylori z podwójną opornością u 62 dzieci (wg 31)
Medicine
(Nazwa leku)
Dosage/24h, 14 days (Dawkowanie/dobę, przez 14 dni)
15–25 kg
25–35 kg
> 35 kg
Esomeprazole
2 × 20 mg
(1.6–2.6 mg/kg)
30 × 20 mg
(1.6–2.0 mg/kg)
2 × 30 mg
(?–1.7 mg/kg)
Amoxicillin
2 × 750 mg
(60–100 mg/kg)
2 × 1000 mg
(57–80 mg/kg)
2 × 1500 mg
(?–85 mg/kg)
Metronidazole
2 × 250 mg
(20–33 mg/kg)
500 × 250 mg
(21–30 mg/kg)
2 × 500 mg
(?–28 mg/kg)
Eradication rate: 73%.
Wskaźnik eradykacji 73%.
Adverse events: nausea (10.8%), diarrhea (8.9%), vomiting (7.1%), abdominalgia (5.4%), headache (3.6%).
Objawy niepożądane: nudności (10,8%), biegunka (*8,9%), wymioty (7,1%), bóle brzucha (5,4%), ból głowy (3,6%).
H. pylori and Increasing Antibiotic Resistance
Increasing H. pylori resistance to clarithromycin and metronidazole forces the introduction of
new drugs and treatment schemes. Triple therapy
composed of a proton pump inhibitor, amoxicillin and clarithromycin is being replaced by quadruple therapy. Clarithromycin is being replaced
679
by newer antibiotics and bismuth salts are being
introduced. The length of treatment is being prolonged from 7 to 10 or 14 days. The principal goal
of these changes is the achievement of the most effective eradication of Helicobacter pylori.
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Address for correspondence:
Franciszek Iwańczak
Department of Pediatrics, Gastroenterology and Nutrition
M. Curie-Skłodowskiej 50/52
50-369 Wrocław
Poland
Tel.: +48 71 770 30 45
E-mail: [email protected]
Conflict of interest: None declared
Received: 4.04.2012
Revised: 27.06.2012
Accepted: 8.10.2012